It is proposed to continue studies in anesthetized dogs, cats and rabbits of the sensory characteristics of vagal and sympathetic afferent nerve fibers arising from the lower respiratory tract, and of the protective and homeostatic reflexes evoked by their stimulation. The afferent studies will be carried out by recording impulses from single fibers of the cervical vagus nerves and the thoracic (T1-T5) rami and chain; they have five main objectives: 1) To further explore the response of rapidly adapting receptors (RARs) to changes in lung compliance (CDYN); and to examine the hypothesis that stimulation of RARs by decreasing CDYN is due to their specific sensitivity to longitudinal stretch of the airways. This hypothesis could explain why RARs are more sensitive than slowly adapting receptors to changes in CDYN. 2) To examine possible differences in the pharmacological response of lower airway C-fibers and RARs to acetylcholine and congeners and to histamine, i.e., to determine whether stimulation is nicotinic or muscarinic in the former case, or represents an H1 or H2 effect in the latter. 3) To examine the response of bronchial C-fibers to inhalation of cigarette smoke, particular irritants and halothane. 4) To examine the sensory properties of nonmyelinated pulmonary vagal fibers, recently identified in this laboratory, that do not appear to belong to any of the known categories of lung afferent. 5) To examine the location and sensory properties of sympathetic afferent fibers arising from the lungs and lower airways. Achievement of goals 1-5 will extend knowledge of the range of sensory information arising from the lower respiratory tract. The reflex studies have four main objectives: 1) To examine the reflex effects on tracheal submucosal gland secretion of delivering cigarette smoke to the lower airways; and to examine the interaction of various excitatory (e.g., lung C-fibers) and inhibitory (pulmonary stretch receptors and group IV muscle afferents) inputs on the reflex control of airway secretion. Secretion will be assessed by counting tantalum-coated secretory "hillocks" in the upper trachea. 2) To determine the effects of stimulating lung sympathetic afferents of airway secretion, tracheal smooth muscle tension and airflow resistance in the lower airways. 3) To determine, in dogs, whether injection of a neutral endopeptidase inhibitor into the bronchial artery will reveal evidence of 'axon reflex' type effects when afferent vagal C-fibers are stimulated antidromically. 4) To examine the neural mechanisms involved in cough induced by intrapulmonary administration of SO2. The functional utility of some reflexes triggered by stimulation of airway afferents in controversial. But, "useful" or not, ventilatory, bronchomotor and bronchosecretory reflexes originating in the airways are important because they may be engaged by disease, particularly of the lower respiratory tract, and may be involved in initiating major components of a disease or in aggravating an already existing disease and the discomfort associated with it.